Near the beginning of the 2nd century ce, Greek physician, writer, and philosopher Galen of Pergamum appears to have coined the term rheumatismos, in which rheuma means “to flow” (an alternative meaning is “phlegm”). A common usage was a “defluxion of rheum” from the nose or mouth. Galen knew that respiratory diseases causing the production of phlegm often resulted in patients developing painful maladies, such as the conditions now described as arthritis and neuropathy. Parisian physician Guillaume de Baillou reintroduced the word rheumatismos to medicine in the 17th century, in a work that was published posthumously (Liber de Rheumatismo et Pleuritide Dorsali; 1642). He used the word to describe a form of muscular rheumatism and to describe what is now known as rheumatic fever. Baillou knew that a respiratory disease called catarrh, which is associated with inflammation of the upper respiratory tract, was connected to rheumatism and that rheumatism was systemic in nature, affecting many parts of the body. The rheumatic maladies as described by Galen and Baillou were later associated with Streptococcus infections.

In the third volume of the first edition of Encyclopædia Britannica; or, A Dictionary of Arts and Sciences, published between 1768 and 1771, the entry on medicine contains a paragraph “of the rheumatism,” in which the authors provide an account of acute rheumatic fever. The description of the condition is similar to that provided in 1666 by British physician Thomas Sydenham in his work Methodus Curandi Febres, Propriis Observationibus Superstructura. In the encyclopaedic discussion, the primary lesion of rheumatic fever and rheumatism is noted: “Its proximate cause seems to be inflammation of the lymphatic arteries.” This determination by early pathophysiologists depicted rheumatic vasculitis, an autoimmunological inflammation of the arterial system. Later in the text, chronic rheumatism is mentioned as “either the remains of a rheumatic fever, or a continuation of pains that proceeded at first from lesser but neglected colds.”

Thus, it appears that the early Scottish and English physicians had determined correctly that rheumatic fever was not only distinct from other respiratory and cardiovascular diseases but also in some instances clearly of infectious etiology. Later advances in knowledge of infectious agents revealed that acute rheumatic fever likely involves high-grade autoimmunological responses to infection with Streptococcus bacteria, whereas lower-grade inflammation may be associated with either chronic infection or lingering affects of acute immunological responses.